PHOX2B p.Ser179=
c.537C>A · rs2153112805 · VCV1132035
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
Haddad syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.044 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2 | GERP -2.3, phastCons 1 |
| Overall | ||
| CADD | 8.659 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,912 alleles
Overall
6.84e-05%
1/1,461,676 alleles · very rare
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- PHOX2B
- Protein
- p.Ser179=
- Coding
- c.537C>A
- MANE Select
- NM_003924
- dbSNP
- rs2153112805
- Type
- single nucleotide variant
- Location
- chr4:41746215 (GRCh38)
- Gene constraint
- LOEUF 0.349 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.94 · 5 PDB
- Residue 179
- the 'disordered' region
Similar variants
- PHOX2B p.Ser179Cys Uncertain significance ★ ⚠ same residue
- PHOX2B c.241+1G>A Likely pathogenic ★★ same condition
- PHOX2B c.242-1G>A Pathogenic/Likely pathogenic ★★ same condition
- PHOX2B p.Arg141Gln Pathogenic/Likely pathogenic ★★ same condition
- PHOX2B p.Tyr83Ter Pathogenic/Likely pathogenic ★★ same condition
- PHOX2B c.241+5G>A Uncertain significance ★★ same condition
- PHOX2B c.241+6G>T Uncertain significance ★★ same condition
- PHOX2B c.429+4C>A Uncertain significance ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/phox2b-p-ser179 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown